rs2933249

Variant names:

• chr3-148698733-G-A
• rs2933249
• NM_000685.5:c.-132+606G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000685.5(AGTR1):​c.-132+606G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,154 control chromosomes in the GnomAD database, including 1,875 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1875 hom., cov: 32)
• Consequence: AGTR1 NM_000685.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105
• Publications: 10 publications found

Genes affected

AGTR1 (HGNC:336): (angiotensin II receptor type 1) Angiotensin II is a potent vasopressor hormone and a primary regulator of aldosterone secretion. It is an important effector controlling blood pressure and volume in the cardiovascular system. It acts through at least two types of receptors. This gene encodes the type 1 receptor which is thought to mediate the major cardiovascular effects of angiotensin II. This gene may play a role in the generation of reperfusion arrhythmias following restoration of blood flow to ischemic or infarcted myocardium. It was previously thought that a related gene, denoted as AGTR1B, existed; however, it is now believed that there is only one type 1 receptor gene in humans. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2020]

AGTR1 Gene-Disease associations (from GenCC):

• renal tubular dysgenesis of genetic origin

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• essential hypertension, genetic

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGTR1	NM_000685.5	c.-132+606G>A		intron_variant	Intron 1 of 2	ENST00000349243.8	NP_000676.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGTR1	ENST00000349243.8	c.-132+606G>A		intron_variant	Intron 1 of 2	1	NM_000685.5	ENSP00000273430.3

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21092 AN: 152036 Hom.: 1877 Cov.: 32

Gnomad AFR AF: 0.0449

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.172

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.139 AC: 21081 AN: 152154 Hom.: 1875 Cov.: 32 AF XY: 0.139 AC XY: 10318 AN XY: 74378

African (AFR) AF: 0.0448 AC: 1860 AN: 41544

American (AMR) AF: 0.129 AC: 1974 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 980 AN: 3472

East Asian (EAS) AF: 0.103 AC: 532 AN: 5176

South Asian (SAS) AF: 0.187 AC: 902 AN: 4814

European-Finnish (FIN) AF: 0.148 AC: 1568 AN: 10568

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12595 AN: 67990

Other (OTH) AF: 0.170 AC: 358 AN: 2104

Alfa AF: 0.120 Hom.: 597

Bravo AF: 0.131

Asia WGS AF: 0.130 AC: 457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.9
DANN	Benign	0.64
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2933249; hg19: chr3-148416520;